In the treatment of chronic liver diseases an adequate therapy can be chosen only in the knowledge of the pathogenetic processes. In liver diseases caused by oxidative stress (alcoholic and non-alcoholic fatty liver and steatohepatitis, drug- and chemical-induced hepatic toxicity) the antioxidant medicines such as silymarin, in chronic hepatitis caused by hepatitis B and hepatitis C virus the combined pegylated interferon and nucleoside analogue treatments are the primary therapeutic modalities of choice. The main effects of silymarin: it exerts membrane-stabilising and antioxidant activity, it promotes hepatocyte regeneration, it reduces inflammatory reaction, and it inhibits fibrinogenesis in the liver. These results have been established by experimental and clinical trials. According to open studies the long-term administration of silymarin significantly increased survival time of patients with alcoholinduced liver cirrhosis. Recently it has been demonstrated that high-dose silibinin infusion treatment could significantly reduce viral load of hepatitis C viruses following four weeks of application. Based on the results of studies using methods of molecular biology, silymarin can significantly reduce tumour cell proliferation, angiogenesis as well as insulin resistance. These results support the administration of silymarin preparations in the treatment of patients with chronic liver diseases, especially alcoholic and non-alcoholic steatohepatitis in the current clinical practice and, as it can be expected, also in the future. In some neoplastic diseases they can be administered as adjuvant therapy as well.
Recently, an increasing amount of data on the connection between neuro-endocrine and immune systems has been gathered. Results of molecular genetic research have provided evidence for a common language of these systems including neurotransmitters, hormones and cytokines. It has been proved that the immune system is capable of producing neurotransmitters and hormones and even the endocrine system can prepare cytokines. This integrative (holistic) approach makes possible the investigation of physiological and pathological events as interactions of psychoneuro-endocrine-immune systems. The associations of autoimmune diseases and the autoimmune polyendocrine syndromes constitute a heterogeneous group of disorders characterised by decreased or lost immune tolerance against self-antigens. Molecular genetic research has explored the mechanism of the associations of diseases that are called organ-specific. Autoimmune polyendocrine syndrome type 1 is characterised by the presence of at least two of the three cardinal diseases: Addison's disease, autoimmune hypoparathyroidism and mucocutaneous candidiasis. This rare autosomal recessive syndrome is induced by mutations of the autoimmune regulator (AIRE) gene. Autoimmune polyendocrine syndrome type 2 that occurs at a much higher frequency is observed and defined as the coexistence of Addison's disease, autoimmune thyroid disease and/or type 1 diabetes mellitus. Autoimmune polyendocrine syndrome type 3 is characterised by an association of autoimmune thyroid disease and type 1 diabetes mellitus. In contrast to autoimmune polyendocrine syndrome type 1, HLA and other antigens have proved to be important in types 2 and 3 of the syndrome. Identification of genetic factors predisposing to these syndromes contributes to our understanding of the common mechanisms involved in autoimmunity and offers a possibility for early treatment and prevention as well.
Due to its antioxidant capacity, the essential trace element selenium exerts complex effects on the endocrine and immune systems. Selenium may have an important role in autoimmune thyroid diseases because levels of free oxygen radicals are elevated during physiological thyroid hormone synthesis.
To determine whether selenium therapy can influence anti-thyroid peroxidase and anti-thyroglobulin antibody levels or if there is a correlation between antioxidant capacity and autoantibody titres.
132 patients with autoimmune thyroiditis were investigated in a prospective, blinded and placebo controlled study. L-thyroxine substitution therapy was administered in both groups and TSH levels remained in the normal range. The selenium treated group (70 patients, 68 female, mean age 41.4 ± 9.5 years) was compared with the placebo treated group (62 patients, 61 female, mean age 42.7 ± 8.3 years). Selenium therapy included oral administration of 100 μg L-seleno-methionine tablets twice a day for a year. Determinations of TSH, fT4 and fT3 as well as antibody levels were carried out by chemoluminescent method. Total antioxidant capacity was determined by Randox kit, and serum selenium levels were measured by atomic absorption technique. In the course of the study patients were controlled every third month and at the end of the one year long observation period.
Selenium levels in untreated patients were significantly lower than those in treated patients and controls. The fT3/fT4 ratio proved to be higher in patients after selenium therapy. Titres of antithyroid antibodies (mostly antithyroid peroxidase) significantly decreased at the end of the study. An inverse correlation was found between antioxidant capacity and antithyroid peroxidase levels. The volume of thyroid gland slightly diminished in treated patients. No adverse reactions were observed.
Selenium completed with L-thyroxine is a suitable therapy of patients with autoimmune thyroiditis.
Non-alcoholic fatty liver disease is present in 15–25% of the general population. The fundamental derangement in non-alcoholic fatty liver disease is insulin resistance, a key component of the metabolic syndrome, which includes type 2 diabetes mellitus, dyslipidemia, hypertension, and obesity. The natural history of non-alcoholic fatty liver disease is not always benign, its causality for chronic liver disease and cirrhosis is well known in clinical practice and sometimes it is accompanied by hepatocellular carcinoma. Non-alcoholic fatty liver disease is likely to be associated with increased cardiovascular disease risk, and raises the possibility that non-alcoholic fatty liver disease may be not only a marker but also an early mediator of atherosclerosis. Therapy is currently directed at treating components of the metabolic syndrome which may also beneficial for the liver.
In the background of hepatic steatosis there is an imbalance between the processes of the hepatocytes’ lipid uptake and lipid elimination, thus overproduction results in the accumulation of excess triglycerides in the cells of the liver. Normally about 5% of the cells contain triglyceride; in steatosis this may exceed 50%. Under 50% the condition is called fatty infiltration, and over 50% it is called fatty liver. In mild forms this does not necessarily lead to disorders in cell functions, but in more severe forms it does; it often precedes the death of the cells. Fatty liver can be considered a pathologic condition which makes the liver more susceptible to other toxic influences. It is not a genuine disease; in most cases it is associated with a noxious state or other pathologic process. By itself, to a certain grade of severity (the appearance of fibrosis), it represents a reversible damage; upon cessation of the underlying cause the liver clears its excess triglyceride content. The treatment is to be aimed at the underlying process; up to now there is no known specific medicine that could reduce the fat accumulated in the hepatocytes.
Interferons are glycoproteins of heterogeneous composition produced by the living cell as a part of the immune response to a viral infection. They were discovered exactly half a century ago. They possess antineoplastic, antiviral and immunomodulatory activities. The therapeutically used forms are denoted by Greek letters indicating their origin: leukocytes, fibroblasts, and lymphocytes for interferon-alpha, -beta and -gamma, respectively. Both natural and recombinant interferons have been used in human medicine. Connection with polyethylene glycol assures the prolonged effect of interferon preparations. Currently they are applied for the elimination of viruses in the therapy of chronic hepatitis B and C and for inhibiting the progression of neoplasms in oncology.
Cardiovascular mortality rate is increasing all over the world. One of the most important aetiological factors of the lethal outcome is diabetes mellitus. Medicines that can be used for treating this disease include agents which increase insulin secretion (insulin secretagogues), enhance the effect of insulin (insulin sensitizers), or inhibit glucose absorption. All these can be used as monotherapy and in various combinations as well. In the practice, the combination of rosiglitazone and glimepiride seems to be very useful. As each component exerts its activity on different target points, they complement each other well. Glimepiride stimulates insulin secretion in the beta cells, and leads to a reduction of blood glucose levels, while rosiglitazone stimulates peroxisome proliferators-activated receptor-gamma and improves insulin resistance at the vascular and metabolically active cells. The combination of glimepiride and rosiglitazone is usually well tolerated by the patients, and the fix combination also improves their adherence to therapy.
A parenchimás szervek – mint például a máj – abnormális zsírfelhalmozódását zsíros átalakulásnak nevezzük. A máj elzsírosodásának hátterében a májsejtek zsírfelvevő és zsírleadó folyamatainak egyensúlyzavara áll, miáltal a felesleges triglicerid felhalmozódik a hepatocytákban. Normál esetben a sejtek kb. 5%-a tartalmaz trigliceridet, zsírmáj esetén ez az érték 50% fölé is emelkedhet. 50% alatt májelzsírosodásról, 50% felett zsírmájról beszélünk. Enyhébb esetben nem feltétlenül okoz sejtműködési zavart, súlyosabb formánál azonban igen, sokszor a sejthalál előfutára. A zsírmáj olyan kórállapotnak tekinthető, mely érzékennyé teszi a májat egyéb toxikus hatásokkal szemben. Nem önálló betegség, legtöbbször valamilyen ártalom, egyéb kórfolyamat kísérő jelensége. Önmagában – bizonyos súlyossági fokig (a fibrosis megjelenéséig) – reverzíbilis károsodást jelent, a kiváltó ok megszűnésekor a máj a felesleges triglicerid-tartalmát leadja. Kezelni az alapfolyamatot kell; még nem ismert olyan specifikus gyógyszer, amely a hepatocytákban lerakódott zsírt csökkenti.